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Patented Feb. 5, 1929.

'UNITED STATES PATENT oer 10E.

ERNST BURCKHABDT, FRITZ MU'LLER, AND ERNST ROTHLIN, OF BASEL, SWITZER- LAND, ASSIGNORS TO THE FIRM OF CHEMICAL WORKS, I'OBMERLY SANDOZ, OI

BASED, SWITZERLAND.

DERIVATIVES OF THE CINGHONA ALKALOIDS.

No Drawing. Application filed November 30, 1927, Serial No. 236,8 7'8, and in Switzerland December Ithas been foundthat valuable derivatives of the cinchona alkaloids may be obtained it these alkaloids are combined with bile acids to form new basic salts. The following bile acids come into consideration for the present purpose: natural bile acids like glycocholic, taurocholic and desoxycholic acid, the product of saponification of taurocholic and glycocholic acid: cholic acid 10 as well as products of transformation of the latter substance: dehydrocholic and apocholic acid. The cincliona alkaloids may be natural or synthetic ones like uinine, cinchonine, dihydroquinine, dihy rocupreineethyl, -isoamyl, or -n-octylether.

These bile acid salts of cinchona alkaloids may be prepared in a known manner by interaction of the bases and the acids or by double decomposition of suitable salts of these substances.

' These new salts possess a stronger antiparasitic action especially on blood parasites than the known salts of cinchona alkaloids.

Examples.

1. 4,2 grammes of methane sulphonate of quinine are'dissolved in 100 com. of water and poured, whilst stirring, into a solution of 4,5 grammes of sodium cholate in com.

Found ,62;

From a solution in urea and aqueous alcohol this salt ma be obtained in fine, colorless crystal nee les on standing for a long time.

II. 4,2 grammes of methane sulphonate of quinine and 4,3 ammes of sodium desoxycholate are a owed to interact as de- 0,2772 grammes neutralized 6,6 0cm 0! 1/10 N H2304 Found Calculated for CnHnNaOnCgH O; N-3,73/

IV. 4,2 grammes of dihydrocupreineethyletherhydrochloride are allowed to interact with'4,5 grammes of sodium cholate' as described. The cholate of dihydrocupreineethylether is a colorless, amorphous powder, showing nearly the same solubility properties as quinine c olate. The analysis of a product dried in a higher vacuum at elevated temperature gave the following result: I

0,2628 grammes neutralized 6,4 com. 01 1/10 N HIS 0 2110 grammes neutralized 5,0 com. 01 1110 N H1804 Calculated (or ClIHZINIOLCMHNOS N-3,56% Found 3,41; 3,32%.

What we claim is: 4

1. As new articles of manufacture, the basic cinchona alkaloid salts of bile acids constitutin amorphous powders easily solu-- 5 powder easily soluble in alcohol, methanol uble in alcohol, methanol and acetone, difli- In witness whereof we have hereunto cultly soluble in ether and water. signed our names this 18th day of November 5. Asha.I new artiole of manufacture, qui- 1927- mne c 0 ate constltutlng an amorphous ERNST BFRCKHARDT.

and acetone, diflicultly soluble in ether and FRITZ MULLER- water. ERNST ROTHLIN. 

